Abstract B08: Genomics analyses of less common epithelial ovarian cancer subtypes.

Media type: E-Article

Title: Abstract B08: Genomics analyses of less common epithelial ovarian cancer subtypes

Contributor: Gorringe, Kylie L.; Wakefield, Matthew; Hunter, Sally M.; Ryland, Georgina L.; Cheasley, Dane; Anglesio, Michael S.; Christie, Michael; Sharma, Raghwa; Yoland, Antill; Rowley, Simone M.; Li, Jason; Gilks, Blake; Allan, Prue E.; Stephens, Andrew N.; Ananda, Sumi; Pyman, Jan; Koebel, Martin; McAlpine, Jessica; Gourley, Charlie; Huntsman, David G.; deFazio, Anna; Bowtell, David DL; Campbell, Ian G.; Scott, Clare

Published: American Association for Cancer Research (AACR), 2016

Language: English

DOI: 10.1158/1557-3265.ovca15-b08

ISSN: 1078-0432; 1557-3265

Keywords: Cancer Research ; Oncology

Origination:

Footnote:

Description: Abstract While the genomics of high-grade serous carcinoma are well-studied in large international consortia, the less common subtypes have been neglected. We have sought to rectify this gap by analyzing international collections of low-grade serous and mucinous ovarian carcinomas and their putative benign and borderline precursors. Exome sequencing and copy number analysis of low-grade serous carcinomas (n=9) and serous borderline tumours (n=13) and targeted sequencing and copy number analysis in additional carcinomas (n=10) and borderline tumours (n=44) identified recurrent mutations in novel drivers such as EIF1AX and USP9X, as well as the known drivers KRAS, BRAF and NRAS. Copy number changes including 9p and 1p losses were significantly associated with progression from borderline to carcinoma. Exome and targeted sequencing analysis of mucinous carcinomas (GAMuT study) found a surprisingly high proportion (~50%) with TP53 mutations, and mutations in new drivers like RNF43 and ELF3. Despite similarities in early RAS/RAF pathway oncogenic drivers and CDKN2A disruption, the genetics of these two subtypes are otherwise distinct, suggesting differing etiologies and selective pressures. We also present here the first whole-genome sequencing analysis of a high-grade mucinous ovarian carcinoma collected from multiple sites at autopsy (CASCADE study). The patient, aged just 41 when diagnosed with Stage I mucinous ovarian carcinoma, had a 26-month progression-free interval, including normal CA125 and CA19-9 measurements at 21 months. The primary tumor was mostly borderline in appearance, with only a small focus of carcinoma. At autopsy, the carcinoma was widespread in the body, and whole-genome sequencing data was obtained from deposits in the omentum, iliac lymph node, para-aortic lymph node and upper diaphragm. These data were compared to the primary ovarian tumor and nine other sites sampled at autopsy. Citation Format: Kylie L. Gorringe, Matthew Wakefield, Sally M. Hunter, Georgina L. Ryland, Dane Cheasley, Michael S. Anglesio, Michael Christie, Raghwa Sharma, Antill Yoland, Simone M. Rowley, Jason Li, Blake Gilks, Prue E. Allan, Andrew N. Stephens, Sumi Ananda, Jan Pyman, Martin Koebel, Jessica McAlpine, Charlie Gourley, David G. Huntsman, Anna deFazio, David DL Bowtell, Ian G. Campbell, Clare Scott. Genomics analyses of less common epithelial ovarian cancer subtypes. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr B08.

Access State: Open Access

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